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Melanie A Thompson,
Judith A Aberg,
Jennifer F Hoy,
Amalio Telenti,
Constance Benson,
Pedro Cahn,
Joseph J Eron,
Huldrych F Günthard,
Scott M Hammer,
Peter Reiss,
Douglas D Richman,
Giuliano Rizzardini,
David L Thomas,
Donna M Jacobsen,
Paul A Volberding
[show abstract]
[hide abstract]
ABSTRACT: New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings.
To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure.
Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus.
Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered.
New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.
JAMA The Journal of the American Medical Association 07/2012; 308(4):387-402. · 30.03 Impact Factor
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JAMA The Journal of the American Medical Association 11/2010; 304(17):1897-1898. · 30.03 Impact Factor
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Jeffrey M Jacobson,
Jacob P Lalezari, Melanie A Thompson,
Carl J Fichtenbaum,
Michael S Saag,
Barry S Zingman,
Paul D'Ambrosio,
Nancy Stambler,
Yakov Rotshteyn,
Andre J Marozsan,
Paul J Maddon,
Stephen A Morris,
William C Olson
[show abstract]
[hide abstract]
ABSTRACT: The anti-CCR5 antibody PRO 140 has shown potent and prolonged antiretroviral activity in subjects infected with CCR5-tropic (R5) HIV-1. Prior studies have examined single intravenous doses ranging up to 5 mg/kg of body weight or up to three subcutaneous doses ranging up to 324 mg. Here we report the results of a randomized, double-blind, placebo-controlled trial that examined the antiviral activity, tolerability, and pharmacokinetics of single 5-mg/kg and 10-mg/kg intravenous infusions of PRO 140 in 31 treated subjects. Eligibility criteria included HIV-1 RNA levels of >5,000 copies/ml, CD4(+) cell counts of >300/μl, no antiretroviral therapy for ≥12 weeks, and detection of only R5 HIV-1 in the original Trofile assay. Following poststudy testing with an enhanced-sensitivity Trofile assay, one subject treated with 10 mg/kg was reclassified as having dual/mixed-tropic virus at screening, and the data for that subject were censored from efficacy analyses. The mean maximum reduction of the HIV-1 RNA level from the baseline level was 1.8 log(10) units for both the 5-mg/kg and 10-mg/kg doses (P < 0.0001 relative to placebo). Viral loads reached their nadir at day 12 posttreatment and remained significantly (P < 0.01) reduced through day 29 for both PRO 140 dose groups. Treatment was generally well tolerated, with no dose-limiting toxicity being observed. Peak serum concentrations and overall exposures increased proportionally with dose. In summary, single 5-mg/kg and 10-mg/kg doses of PRO 140 exhibited potent, long-lived antiviral activity and were generally well tolerated. The findings further delineate the safety and antiviral properties of this novel, long-acting antiretroviral agent.
Antimicrobial Agents and Chemotherapy 10/2010; 54(10):4137-42. · 4.84 Impact Factor
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Melanie A Thompson,
Judith A Aberg,
Pedro Cahn,
Julio S G Montaner,
Giuliano Rizzardini,
Amalio Telenti,
José M Gatell,
Huldrych F Günthard,
Scott M Hammer,
Martin S Hirsch,
Donna M Jacobsen,
Peter Reiss,
Douglas D Richman,
Paul A Volberding,
Patrick Yeni,
Robert T Schooley
[show abstract]
[hide abstract]
ABSTRACT: Recent data regarding the consequences of untreated human immunodeficiency virus (HIV) infection and the expansion of treatment choices for antiretroviral-naive and antiretroviral-experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adults with HIV infection.
To provide updated recommendations for management of HIV-infected adults, using antiretroviral drugs and laboratory monitoring tools available in the international, developed-world setting. This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing.
A panel with expertise in HIV research and clinical care reviewed relevant data published or presented at selected scientific conferences since the last panel report through April 2010. Data were identified through a PubMed search, review of scientific conference abstracts, and requests to antiretroviral drug manufacturers for updated clinical trials and adverse event data.
New evidence was reviewed by the panel. Recommendations were drafted by section writing committees and reviewed and edited by the entire panel. The quality and strength of the evidence were rated and recommendations were made by full panel consensus.
Patient readiness for treatment should be confirmed before initiation of antiretroviral treatment. Therapy is recommended for asymptomatic patients with a CD4 cell count < or = 500/microL, for all symptomatic patients, and those with specific conditions and comorbidities. Therapy should be considered for asymptomatic patients with CD4 cell count > 500/microL. Components of the initial and subsequent regimens must be individualized, particularly in the context of concurrent conditions. Patients receiving antiretroviral treatment should be monitored regularly; treatment failure should be detected and managed early, with the goal of therapy, even in heavily pretreated patients, being HIV-1 RNA suppression below commercially available assay quantification limits.
JAMA The Journal of the American Medical Association 07/2010; 304(3):321-33. · 30.03 Impact Factor
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Jeffrey M Jacobson, Melanie A Thompson,
Jacob P Lalezari,
Michael S Saag,
Barry S Zingman,
Paul D'Ambrosio,
Nancy Stambler,
Yakov Rotshteyn,
Andre J Marozsan,
Paul J Maddon,
Stephen A Morris,
William C Olson
[show abstract]
[hide abstract]
ABSTRACT: PRO 140 is a humanized CCR5 monoclonal antibody that has demonstrated potent antiviral activity when it is administered intravenously to adults infected with CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1). This study is the first to evaluate subcutaneous administration.
A randomized, double-blind, placebo-controlled study was conducted among 44 subjects with HIV-1 RNA levels of >5000 copies/mL, CD4(+) cell counts of >300 cells/microL, no receipt of antiretroviral therapy for >or=12 weeks, and only R5 HIV-1 detectable. Subjects received placebo, 162 mg of PRO 140, or 324 mg of PRO 140 weekly for 3 weeks or 324 mg of PRO 140 every other week for 2 doses by means of subcutaneous infusion. Subjects were monitored for 58 days for safety, antiviral effects, and PRO 140 serum concentrations.
Subcutaneous PRO 140 demonstrated potent and prolonged antiretroviral activity. Mean log(10) reductions in HIV-1 RNA level were 0.23, 0.99 (P=.009), 1.37 (P<.001), and 1.65 (P<.001) for the placebo, 162 mg weekly, 324 mg biweekly, and 324 mg weekly dose groups, respectively. Viral loads remained suppressed between successive doses. Treatment was generally well tolerated.
This trial demonstrates proof of concept for a monoclonal antibody administered subcutaneously in HIV-1 infected individuals. Subcutaneous PRO 140 offers the potential for significant dose-dependent HIV-1 RNA suppression and infrequent patient self-administration.
ClinicalTrials.gov identifier: NCT00642707 .
The Journal of Infectious Diseases 04/2010; 201(10):1481-7. · 6.41 Impact Factor
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Jeffrey M Jacobson,
Michael S Saag, Melanie A Thompson,
Margaret A Fischl,
Ralph Liporace,
Richard C Reichman,
Robert R Redfield,
Carl J Fichtenbaum,
Barry S Zingman,
Mahesh C Patel, [......],
Marti Michael,
Hans Kroger,
Hieu Ly,
Yakov Rotshteyn,
Robert Buice,
Stephen A Morris,
Joseph J Stavola,
Paul J Maddon,
Alton B Kremer,
William C Olson
[show abstract]
[hide abstract]
ABSTRACT: The current goal of human immunodeficiency virus type 1 (HIV-1) therapy is to maximally suppress viral replication. Securing this goal requires new drugs and treatment classes. The chemokine receptor CCR5 provides an entry portal for HIV-1, and PRO 140 is a humanized monoclonal antibody that binds to CCR5 and potently inhibits CCR5-tropic (R5) HIV-1 in vitro.
A randomized, double-blind, placebo-controlled, dose-escalating study was conducted in 39 individuals with HIV-1 RNA levels or =5000 copies/mL, CD4(+) cell counts > or =250 cells/microL, no antiretroviral therapy for 3 months, and only R5 HIV-1 detectable. Cohorts were randomized 3:10 to receive placebo or doses of PRO 140 of 0.5, 2, or 5 mg/kg. Subjects were monitored for 58 days for safety, antiviral effects, and serum concentrations of PRO 140.
PRO 140 was generally well tolerated and demonstrated potent, rapid, prolonged, and dose-dependent antiviral activity. Mean reductions in HIV-1 RNA level of 0.58 log(10), 1.20 log(10) (P= .0002) and 1.83 log(10) (P= .0001) were observed for the 0.5-, 2-, and 5-mg/kg dose groups, respectively. Reductions in mean viral load of > or =10-fold were observed within 4 days and persisted for 2-3 weeks after treatment.
This trial established clear proof of concept for PRO 140 as a potent antiretroviral agent with extended activity after a single dose.
ISRCTN Register: ISRCTN45537485 .
The Journal of Infectious Diseases 10/2008; 198(9):1345-52. · 6.41 Impact Factor
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Scott M Hammer,
Joseph J Eron,
Peter Reiss,
Robert T Schooley, Melanie A Thompson,
Sharon Walmsley,
Pedro Cahn,
Margaret A Fischl,
Jose M Gatell,
Martin S Hirsch,
Donna M Jacobsen,
Julio S G Montaner,
Douglas D Richman,
Patrick G Yeni,
Paul A Volberding
[show abstract]
[hide abstract]
ABSTRACT: The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection.
To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients.
A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified.
Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus.
New data and considerations support initiating therapy before CD4 cell count declines to less than 350/microL. In patients with 350 CD4 cells/microL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100,000 copies/mL) and rapidly declining CD4 cell count (>100/microL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.
JAMA The Journal of the American Medical Association 08/2008; 300(5):555-70. · 30.03 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To evaluate the pharmacodynamics and safety of escalating doses of amdoxovir (DAPD) monotherapy administered to treatment-naive and experienced HIV-1-infected patients over 15 days.
Ninety patients with plasma HIV-1 RNA levels between 5000 and 250,000 copies/ml were randomized to DAPD 25, 100, 200, 300 or 500 mg twice daily or 600 mg once daily monotherapy [antiretroviral therapy (ART)-naive and ART-experienced] or to add DAPD 300 or 500 mg twice daily to existing ART. After 15 days of dosing, patients were followed for an additional 7 days.
Antiviral activity was compared between treatment arms using log10 HIV-1 RNA based on average area under the curve minus baseline to day 15. Safety and tolerability was analyzed by incidence of grade 1 to 4 clinical and laboratory adverse events.
In ART-naive patients receiving short-term DAPD monotherapy, a median reduction in plasma HIV-1 RNA of 1.5 log10 copies/ml at the highest doses was observed. In ART-experienced patients, the reduction in viral load observed at each dose was less than that observed in treatment-naive patients (reduction of 0.7 log10 at 500 mg twice daily). The incidence of adverse events was similar across groups with the majority of adverse events reported as mild or moderate in severity. Steady-state plasma concentrations of DAPD and dioxolane guanosine followed linear kinetics.
DAPD was well tolerated and produced antiviral activity in treatment-naive and in some treatment-experienced patients. In ART-experienced patients, the antiviral activity was significant in those with no thymidine-analogue mutations and higher baseline CD4+ cell counts.
AIDS 11/2005; 19(15):1607-15. · 6.24 Impact Factor
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Patrick G Yeni,
Scott M Hammer,
Martin S Hirsch,
Michael S Saag,
Mauro Schechter,
Charles C J Carpenter,
Margaret A Fischl,
Jose M Gatell,
Brian G Gazzard,
Donna M Jacobsen,
David A Katzenstein,
Julio S G Montaner,
Douglas D Richman,
Robert T Schooley, Melanie A Thompson,
Stefano Vella,
Paul A Volberding
[show abstract]
[hide abstract]
ABSTRACT: Substantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection.
To update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails.
Evidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management.
Evidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004.
Data were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached.
Four antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel).
Further insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.
JAMA The Journal of the American Medical Association 08/2004; 292(2):251-65. · 30.03 Impact Factor
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[show abstract]
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ABSTRACT: To establish the clinical equivalence (noninferiority) of one tablet containing abacavir 300 mg-lamivudine 150 mg-zidovudine 300 mg (Trizivir) versus a tablet containing lamivudine 150 mg-zidovudine 300 mg (Combivir) given with one abacavir (ABC) 300-mg tablet, administered twice/day, in antiretroviral-experienced, human immunodeficiency virus (HIV)-1-infected patients.
Randomized, open-label, parallel-group, multicenter, formulation-switch study.
Twenty seven outpatient treatment sites.
Adults with HIV-1 RNA levels of 400 copies/ml or less and CD4+ cell counts above 200 cells/mm3 who had been treated for 16 weeks or more with highly active antiretroviral therapy containing Combivir-ABC.
Patients were randomized 1:1 to Trizivir (97 patients) or Combivir-ABC (98) for 24 weeks.
The primary study end point was the proportion of patients who maintained less than a 0.5-log10 increase from baseline in HIV-1 RNA (virologic success) through week 24. Clinical equivalence of the treatments was established if the 95.1% lower confidence limit (LCL) for the difference in proportion of virologic success with Trizivir minus Combivir-ABC was -0.12 or greater. Trizivir was clinically equivalent to Combivir-ABC. The intent-to-treat observed analysis at week 24 with Trizivir and Combivir-ABC showed a similar rate of virologic success (83% [80/97] and 77% [75/98], respectively, 95.1% LCL -0.026), of patients with HIV-1 RNA levels of 400 or fewer copies/ml (99% [82/83] and 93% [77/83], respectively, 95.1% LCL 0.021), and of patients with HIV-1 RNA levels of fewer than 50 copies/ml (89% [74/83] and 77% [64/83], respectively, 95.1% LCL 0.038). The intent-to-treat missing = failure analysis showed comparable results. Changes in CD4+ cell count from baseline, overall mean self-reported adherence (Trizivir 97%, Combivir-ABC 92%), and adverse events did not differ significantly between treatments. No ABC-related hypersensitivity reactions occurred.
Trizivir was clinically equivalent to Combivir-ABC and may be substituted for the latter to simplify treatment and reduce pill burden.
Pharmacotherapy 12/2003; 23(11):1432-40. · 2.90 Impact Factor
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M Keith Rawlings, Melanie A Thompson,
Charles F Farthing,
Lawrence S Brown,
Joseph Racine,
Robert C Scott,
Karen H Crawford,
S Diane Goodwin,
Jerry M Tolson,
Vanessa C Williams,
Mark S Shaefer
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ABSTRACT: A 24-week open-label clinical trial was conducted in 195 HIV-infected adults commonly underrepresented in research (35% female, 71% African American, 21% Hispanic, and 20% injection drug users [IDUs]) to evaluate the effect of an HIV educational program on efficacy and adherence with a simple, compact, twice-daily triple nucleoside regimen containing a lamivudine (150 mg)/zidovudine (300 mg) combination (COM) tablet plus abacavir (ABC), 300 mg. At baseline, the patients' median plasma HIV-1 RNA level was 4.18 log10 copies/mL and the median CD4+ cell count was 379 cells/mm3. Patients were randomized 1:1 to 4 modules of the Tools for Health and Empowerment HIV education intervention plus routine counseling (EI + RC; n = 96) or to routine counseling alone (RC; n = 99). No differences between the EI + RC and RC treatment arms were observed with respect to the proportion of patients achieving plasma HIV-1 RNA levels <40 copies/mL (60% [33/55] vs. 55% [38/69]; P = 0.529) or <400 copies/mL (80% [44/55] vs. 80% [55/69]; P = 0.689) at week 24 (intent-to-treat observed analysis), increase in median CD4 cell count above baseline at week 24 (78.3 vs. 104.8 cells/mm3; P = 0.498), or mean overall adherence rates as measured by the Medication Event Monitoring System (MEMS) (70% vs. 74%). COM + ABC was generally well tolerated, and no association was observed between interruptions in treatment and the development of ABC hypersensitivity (5 suspected cases). In conclusion, in underrepresented patients, the EI used in this study did not affect the efficacy and adherence results with ABC + COM to any greater degree than did RC.
JAIDS Journal of Acquired Immune Deficiency Syndromes 10/2003; 34(2):174-83. · 4.43 Impact Factor
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ABSTRACT: A 48-week open-label study of 11 antiretroviral-naive, human immunodeficiency virus type 1 (HIV-1)-infected adults evaluated once-daily treatment with adefovir dipivoxil, lamivudine, didanosine, and efavirenz. At baseline, the median plasma HIV-1 RNA level was 4.99 log(10) copies/mL, and the median CD4 cell count was 471 cells/mm(3). At 24 and 48 weeks after initiation of treatment, median HIV-1 RNA levels decreased from baseline by 4.77 and 4.99 log(10) copies/mL, respectively, and median CD4 cell counts increased by 135 and 177 cells/mm(3), respectively. The regimen was generally well tolerated. No patients withdrew from the study because of adverse events. However, 7 patients developed adefovir-related nephrotoxicity after >/=20 weeks of treatment; this resolved without sequelae after adefovir was discontinued. Overall adherence was 85%. Once-daily quadruple-drug therapy with adefovir, lamivudine, didanosine, and efavirenz provides pronounced and durable suppression of HIV-1 RNA and elevation of CD4 cell counts over the course of 48 weeks, with generally good tolerability and adherence.
The Journal of Infectious Diseases 10/2002; 186(7):1028-33. · 6.41 Impact Factor
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Patrick G Yeni,
Scott M Hammer,
Charles C J Carpenter,
David A Cooper,
Margaret A Fischl,
Jose M Gatell,
Brian G Gazzard,
Martin S Hirsch,
Donna M Jacobsen,
David A Katzenstein,
Julio S G Montaner,
Douglas D Richman,
Michael S Saag,
Mauro Schechter,
Robert T Schooley, Melanie A Thompson,
Stefano Vella,
Paul A Volberding
[show abstract]
[hide abstract]
ABSTRACT: New information warrants updated recommendations for the 4 central issues in antiretroviral therapy: when to start, what drugs to start with, when to change, and what to change to. These updated recommendations are intended to guide practicing physicians actively involved in human immunodeficiency virus (HIV)- and acquired immunodeficiency syndrome (AIDS)-related care.
In 1995, physicians with specific expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care were invited by the International AIDS Society-USA to serve on a volunteer panel. In 1999, others were invited to broaden international representation. The 17-member panel met regularly in closed meetings between its last report in 2000 and April 2002 to review current data. The effort was sponsored and funded by the International AIDS Society-USA, a not-for-profit physician education organization. EVIDENCE AND CONSENSUS PROCESS: The full panel was convened in late 2000 and assigned 7 section committees. A section writer and 3 to 5 section committee members (each panel member served on numerous sections) identified relevant evidence and prepared draft recommendations. Basic science, clinical research, and epidemiologic data from the published literature and abstracts from recent (within 2 years) scientific conferences were considered by strength of evidence. Extrapolations from basic science data and expert opinion of the panel members were included as evidence. Draft sections were combined and circulated to the entire panel and discussed in a series of full-panel conference calls until consensus was reached. Final recommendations represent full consensus agreement of the panel.
Because of increased awareness of the activity and toxicity of current drugs, the threshold for initiation of therapy has shifted to a later time in the course of HIV disease. However, the optimal time to initiate therapy remains imprecisely defined. Availability of new drugs has broadened options for therapy initiation and management of treatment failure, which remains a difficult challenge.
JAMA The Journal of the American Medical Association 08/2002; 288(2):222-35. · 30.03 Impact Factor
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ABSTRACT: Evaluate efficacy and tolerability of lopinavir/ritonavir (LPV/r) plus stavudine and lamivudine long term in antiretroviral-naïve patients.
Open-label follow-up of prospective, randomized, multicenter trial.
Antiretroviral-naïve HIV-infected subjects (N = 00) received of 3 doses of LPV/r plus stavudine and lamivudine for 48 weeks then received LPV/r soft-gel capsules 400/00 mg plus stavudine and lamivudine. After 6 years, subjects replaced stavudine with tenofovir.
At 7 years, by intent-to-treat analysis, 61 % had plasma HIV-RNA <400 copies/mL and 59% had < 50 copies/mL. Thirty-nine subjects discontinued treatment due to adverse events (n = 6), personal/other reasons (0), loss to follow-up (9), and noncompliance (4). Among 28 subjects qualifying for drug resistance testing, no protease inhibitor or stavudine resistance was observed and 4 showed lamivudine resistance. Most common drug-related moderate or severe adverse events were diarrhea (28%), nausea (6%), and abdominal pain (11 %). Subjects who received stavudine (median 6.6 years) and switched to tenofovir demonstrated significant improvements in total cholesterol (p = .009), triglycerides (p = .023), apolipoprotein C-III (p < .001 ), adiponectin (p = .008), fasting insulin (p = .04), and leptin (p = .03).
LPV/r-based therapy demonstrated sustained efficacy with no protease inhibitor or stavudine resistance through 7 years in antiretroviral-naïve patients. Switching from stavudine to tenofovir resulted in significant improvements in multiple metabolic parameters.
HIV Clinical Trials 9(1):1-10. · 1.64 Impact Factor
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Scott M Hammer,
Michael S Saag,
Mauro Schechter,
Julio S G Montaner,
Robert T Schooley,
Donna M Jacobsen, Melanie A Thompson,
Charles C J Carpenter,
Margaret A Fischl,
Brian G Gazzard,
Jose M Gatell,
Martin S Hirsch,
David A Katzenstein,
Douglas D Richman,
Stefano Vella,
Patrick G Yeni,
Paul A Volberding
[show abstract]
[hide abstract]
ABSTRACT: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field.
To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described.
A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel.
Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel.
Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.
Topics in HIV medicine: a publication of the International AIDS Society, USA 14(3):827-43.
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Patrick G. Yeni,
Scott M. Hammer,
Martin S. Hirsch,
Michael S. Saag,
Mauro Schechter,
Charles C. J. Carpenter,
Margaret A. Fischl,
Jose M. Gatell,
Brian G. Gazzard,
Donna M. Jacobsen,
David A. Katzenstein,
Julio S. G. Montaner,
Douglas D. Richman,
Robert T. Schooley, Melanie A. Thompson,
Stefano Vella,
Paul A. Volberding
JAMA The Journal of the American Medical Association 292(2):251-265. · 30.03 Impact Factor
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Charles C. J. Carpenter,
Margaret A. Fischl,
Scott M. Hammer,
Martin S. Hirsch,
Donna M. Jacobsen,
David A. Katzenstein,
Julio S. G. Montaner,
Douglas D. Richman,
Michael S. Saag,
Robert T. Schooley, Melanie A. Thompson,
Stefano Vella,
Patrick G. Yeni,
Paul A. Volberding
[show abstract]
[hide abstract]
ABSTRACT: Objective.
—To provide clinical recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease with currently (mid 1996) available drugs. When to start therapy, what to start with, when to change, and what to change to were addressed.
JAMA The Journal of the American Medical Association 276(2):146-154. · 30.03 Impact Factor
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Scott M. Hammer,
Joseph J. Eron,
Peter Reiss,
Robert T. Schooley, Melanie A. Thompson,
Sharon Walmsley,
Pedro Cahn,
Margaret A. Fischl,
Jose M. Gatell,
Martin S. Hirsch,
Donna M. Jacobsen,
Julio S. G. Montaner,
Douglas D. Richman,
Patrick G. Yeni,
Paul A. Volberding
JAMA The Journal of the American Medical Association 300(5):555-570. · 30.03 Impact Factor
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Scott M. Hammer,
Joseph J. Eron Jr,
Peter Reiss,
Robert T. Schooley, Melanie A. Thompson,
Sharon Walmsley,
Pedro Cahn,
Margaret A. Fischl,
Jose M. Gatell,
Martin S. Hirsch,
Donna M. Jacobsen,
Julio S. G. Montaner
